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1.
J Neurosci ; 41(15): 3307-3319, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33500277

RESUMO

Golgi cells, together with granule cells and mossy fibers, form a neuronal microcircuit regulating information transfer at the cerebellum input stage. Despite theoretical predictions, little was known about long-term synaptic plasticity at Golgi cell synapses. Here, we have used whole-cell patch-clamp recordings and calcium imaging to investigate long-term synaptic plasticity at excitatory synapses impinging on Golgi cells. In acute mouse cerebellar slices, mossy fiber theta-burst stimulation (TBS) could induce either long-term potentiation (LTP) or long-term depression (LTD) at mossy fiber-Golgi cell and granule cell-Golgi cell synapses. This synaptic plasticity showed a peculiar voltage dependence, with LTD or LTP being favored when TBS induction occurred at depolarized or hyperpolarized potentials, respectively. LTP required, in addition to NMDA channels, activation of T-type Ca2+ channels, while LTD required uniquely activation of L-type Ca2+ channels. Notably, the voltage dependence of plasticity at the mossy fiber-Golgi cell synapses was inverted with respect to pure NMDA receptor-dependent plasticity at the neighboring mossy fiber-granule cell synapse, implying that the mossy fiber presynaptic terminal can activate different induction mechanisms depending on the target cell. In aggregate, this result shows that Golgi cells show cell-specific forms of long-term plasticity at their excitatory synapses, that could play a crucial role in sculpting the response patterns of the cerebellar granular layer.SIGNIFICANCE STATEMENT This article shows for the first time a novel form of Ca2+ channel-dependent synaptic plasticity at the excitatory synapses impinging on cerebellar Golgi cells. This plasticity is bidirectional and inverted with respect to NMDA receptor-dependent paradigms, with long-term depression (LTD) and long-term potentiation (LTP) being favored at depolarized and hyperpolarized potentials, respectively. Furthermore, LTP and LTD induction requires differential involvement of T-type and L-type voltage-gated Ca2+ channels rather than the NMDA receptors alone. These results, along with recent computational predictions, support the idea that Golgi cell plasticity could play a crucial role in controlling information flow through the granular layer along with cerebellar learning and memory.


Assuntos
Canais de Cálcio Tipo L/metabolismo , Células Cerebelares de Golgi/metabolismo , Potenciais Pós-Sinápticos Excitadores , Potenciação de Longa Duração , Animais , Células Cerebelares de Golgi/fisiologia , Feminino , Masculino , Camundongos , Fibras Nervosas/metabolismo , Fibras Nervosas/fisiologia , Receptores de N-Metil-D-Aspartato/metabolismo , Sinapses/metabolismo , Sinapses/fisiologia
2.
Dig Liver Dis ; 38(9): 652-8, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16916632

RESUMO

BACKGROUND: Tissue transglutaminase, the coeliac autoantigen, was shown to localise in the enterocytes of coeliac patients and controls. It was speculated that surface tissue transglutaminase has a role in the pathogenesis of coeliac disease. AIMS: To study localisation of tissue transglutaminase in different stages of coeliac disease and other enteropathies with and without villous flattening. METHODS: Immunofluorescent and immunoblotting assays were used. Duodenal cryostat sections from 23 coeliac patients (10 untreated, 8 treated, 5 potential) and 18 controls (2 autoimmune enteropathy and 16 normal duodenal mucosa) were incubated with an anti-tissue transglutaminase monoclonal antibody. Slides were blindly examined. RESULTS: The immunofluorescent assay showed that monoclonal antibody localised in the subepithelial layer, in the lamina propria, and in the pericryptal connective tissue of all samples. It also bound to surface enterocytes in 8/10 untreated, 1/8 treated, and 3/5 potential coeliac patients. None of the controls showed an epithelial distribution of tissue transglutaminase. Immunoblotting experiments performed in enterocytes freshly isolated from duodenal biopsy confirmed these findings. CONCLUSION: Epithelial distribution of tissue transglutaminase is specific for coeliac disease rather than due to a non-specific mucosal inflammation. Analysis of different stages of coeliac disease suggests that the epithelial distribution of tissue transglutaminase is gluten dependent.


Assuntos
Doença Celíaca/metabolismo , Enterócitos/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Transglutaminases/metabolismo , Adulto , Idoso , Biópsia , Estudos de Casos e Controles , Doença Celíaca/dietoterapia , Doença Celíaca/patologia , Duodeno/metabolismo , Duodeno/patologia , Feminino , Imunofluorescência , Glutens , Humanos , Immunoblotting , Mucosa Intestinal/metabolismo , Masculino , Pessoa de Meia-Idade , Proteína 2 Glutamina gama-Glutamiltransferase
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